A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing

Author:

Gordon David E.,Jang Gwendolyn M.ORCID,Bouhaddou MehdiORCID,Xu JieweiORCID,Obernier KirstenORCID,O’Meara Matthew J.ORCID,Guo Jeffrey Z.,Swaney Danielle L.ORCID,Tummino Tia A.ORCID,Hüttenhain RuthORCID,Kaake Robyn M.ORCID,Richards Alicia L.ORCID,Tutuncuoglu BerilORCID,Foussard Helene,Batra JyotiORCID,Haas KelseyORCID,Modak MayaORCID,Kim MinkyuORCID,Haas PaigeORCID,Polacco Benjamin J.ORCID,Braberg HannesORCID,Fabius Jacqueline M.,Eckhardt ManonORCID,Soucheray MargaretORCID,Bennett Melanie J.,Cakir MerveORCID,McGregor Michael JORCID,Li QiongyuORCID,Naing Zun Zar ChiORCID,Zhou YuanORCID,Peng Shiming,Kirby Ilsa T.ORCID,Melnyk James E.ORCID,Chorba John S.ORCID,Lou KevinORCID,Dai Shizhong A.ORCID,Shen WenqiORCID,Shi YingORCID,Zhang ZiyangORCID,Barrio-Hernandez InigoORCID,Memon DanishORCID,Hernandez-Armenta ClaudiaORCID,Mathy Christopher J.P.ORCID,Perica TinaORCID,Pilla Kala B.ORCID,Ganesan Sai J.ORCID,Saltzberg Daniel J.ORCID,Ramachandran RakeshORCID,Liu Xi,Rosenthal Sara B.ORCID,Calviello LorenzoORCID,Venkataramanan SrivatsORCID,Lin YizhuORCID,Wankowicz Stephanie A.ORCID,Bohn MarkusORCID,Trenker RaphaelORCID,Young Janet M.ORCID,Cavero DevinORCID,Hiatt JoeORCID,Roth TheoORCID,Rathore UjjwalORCID,Subramanian AdvaitORCID,Noack Julia,Hubert Mathieu,Roesch Ferdinand,Vallet Thomas,Meyer Björn,White Kris M.ORCID,Miorin LisaORCID,Agard DavidORCID,Emerman MichaelORCID,Ruggero DavideORCID,García-Sastre AdolfoORCID,Jura NataliaORCID,Zastrow Mark vonORCID,Taunton JackORCID,Schwartz OlivierORCID,Vignuzzi MarcoORCID,d’Enfert ChristopheORCID,Mukherjee ShaeriORCID,Jacobson Matt,Malik Harmit S.ORCID,Fujimori Danica G.ORCID,Ideker TreyORCID,Craik Charles S.ORCID,Floor StephenORCID,Fraser James S.ORCID,Gross JohnORCID,Sali AndrejORCID,Kortemme TanjaORCID,Beltrao PedroORCID,Shokat KevanORCID,Shoichet Brian K.ORCID,Krogan Nevan J.ORCID

Abstract

ABSTRACTAn outbreak of the novel coronavirus SARS-CoV-2, the causative agent of COVID-19 respiratory disease, has infected over 290,000 people since the end of 2019, killed over 12,000, and caused worldwide social and economic disruption1,2. There are currently no antiviral drugs with proven efficacy nor are there vaccines for its prevention. Unfortunately, the scientific community has little knowledge of the molecular details of SARS-CoV-2 infection. To illuminate this, we cloned, tagged and expressed 26 of the 29 viral proteins in human cells and identified the human proteins physically associated with each using affinity-purification mass spectrometry (AP-MS), which identified 332 high confidence SARS-CoV-2-human protein-protein interactions (PPIs). Among these, we identify 66 druggable human proteins or host factors targeted by 69 existing FDA-approved drugs, drugs in clinical trials and/or preclinical compounds, that we are currently evaluating for efficacy in live SARS-CoV-2 infection assays. The identification of host dependency factors mediating virus infection may provide key insights into effective molecular targets for developing broadly acting antiviral therapeutics against SARS-CoV-2 and other deadly coronavirus strains.

Publisher

Cold Spring Harbor Laboratory

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